Retinal Degeneration Reduces Consistency of Network-Mediated Responses Arising in Ganglion Cells to Electric Stimulation

IEEE Trans Neural Syst Rehabil Eng. 2020 Sep;28(9):1921-1930. doi: 10.1109/TNSRE.2020.3003345. Epub 2020 Jun 18.

Abstract

Retinal prostheses use periodic repetition of electrical stimuli to form artificial vision. To enhance the reliability of evoked visual percepts, repeating stimuli need to evoke consistent spiking activity in individual retinal ganglion cells (RGCs). However, it is not well known whether outer retinal degeneration alters the consistency of RGC responses. Hence, here we systematically investigated the trial-to-trial variability in network-mediated responses as a function of the degeneration level. We patch-clamp recorded spikes in ON and OFF types of alpha RGCs from r d10 mice at four different postnatal days (P15, P19, P31, and P60), representing distinct stages of degeneration. To assess the consistency of responses, we analyzed variances in spike count and timing across repeats of the same stimulus delivered multiple times. We found the trial-to-trial variability of network-mediated responses increased considerably as the disease progressed. Compared to responses taken before degeneration onset, those of degenerate retinas showed up to ~70% higher variability (Fano Factor) in spike counts (p < 0.001) and ~95% lower correlation level in spike timing (p < 0.001). These results indicate consistency weakens significantly in electrically-evoked network-mediated responses and therefore raise concerns about the ability of microelectronic retinal implants to elicit consistent visual percepts at advanced stages of retinal degeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials
  • Animals
  • Electric Stimulation
  • Mice
  • Photic Stimulation
  • Reproducibility of Results
  • Retinal Degeneration*
  • Visual Prosthesis*